H. Charles Manning, Ph.D.
Associate Professor of Radiology and Radiological Sciences
Associate Professor of Biomedical Engineering
Associate Professor of Neurological Surgery
Director of Molecular Imaging Research; Center for Molecular Probes
Vanderbilt University Institute of Imaging Science
1161 21st. Avenue South
MCN AAA-3115 VUIIS
Nashville, TN 37232-2310
Molecular imaging, chemistry, small-molecule discovery, therapeutic efficacy screening, clinical trial modeling, imaging probe development, imaging validation
Our multi-disciplinary research program involves the development, validation, and translation of non-invasive molecular imaging metrics to assess disease progression and response to therapy. Projects within our program emphasize molecular imaging of cancer, and notably imaging-based assessment of response to anti-cancer pharmaceuticals in colorectal and breast cancer. We are actively engaged in advancing novel methods to image molecular events in both humans and animal models that include receptor expression, proliferation, angiogenesis, and apoptosis. Among these methods include validation of imaging probes for novel applications, as well as high-throughput small-molecule discovery to develop novel imaging compounds.
- McKinley, ET, Zhao, P, Coffey, RJ, Washington, MK, Manning, HC 3''-Deoxy-3''-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer. PLoS One, 9(9), e108193, 2014.
- Hight, MR, Cheung, YY, Nickels, ML, Dawson, ES, Zhao, P, Saleh, S, Buck, JR, Tang, D, Washington, MK, Coffey, RJ, Manning, HC A Peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells. Clin Cancer Res, 20(8), 2126-35, 2014.
- Cheung, YY, Nickels, ML, Tang, D, Buck, JR, Manning, HC Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[(18)F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer. Bioorg Med Chem Lett, 24(18), 4466-71, 2014.
- Powell, AE, Vlacich, G, Zhao, ZY, McKinley, ET, Washington, MK, Manning, HC, Coffey, RJ Inducible Loss of One Apc Allele in Lrig1-Expressing Progenitor Cells Results in Multiple Distal Colonic Tumors with Features of Familial Adenomatous Polyposis. Am J Physiol Gastrointest Liver Physiol, 2014.
- Uddin, MI, Buck, JR, Schulte, ML, Tang, D, Saleh, SA, Cheung, YY, Harp, J, Manning, HC Microwave-assisted, one-pot reaction of 7-azaindoles and aldehydes: a facile route to novel di-7-azaindolylmethanes. Tetrahedron Lett, 55(1), 2014.
- Han, W, Zaynagetdinov, R, Yull, FE, Polosukhin, VV, Gleaves, LA, Tanjore, H, Young, LR, Peterson, TE, Manning, HC, Prince, LS, Blackwell, TS Molecular Imaging of Folate Receptor Beta Positive Macrophages During Acute Lung Inflammation. Am J Respir Cell Mol Biol, 2014.
- Perrone, MG, Malerba, P, Uddin, MJ, Vitale, P, Panella, A, Crews, BC, Daniel, CK, Ghebreselasie, K, Nickels, M, Tantawy, MN, Manning, HC, Marnett, LJ, Scilimati, A PET radiotracer [(18)F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation. Eur J Med Chem, 80C562-568, 2014.
- Tang, D, Nickels, ML, Tantawy, MN, Buck, JR, Manning, HC Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in Glioma. Mol Imaging Biol, 2014.
- Whisenant, JG, McIntyre, JO, Peterson, TE, Kang, H, S¿¿nchez, V, Manning, HC, Arteaga, CL, Yankeelov, TE Utility of [(18)¿¿¿F]FLT-PET to Assess Treatment Response in Trastuzumab-Resistant and Trastuzumab-Sensitive HER2-Overexpressing Human Breast Cancer Xenografts. Mol Imaging Biol, 2014.
- McKinley, ET, Smith, RA, Zhao, P, Fu, A, Saleh, SA, Uddin, MI, Washington, MK, Coffey, RJ, Manning, HC 3''-Deoxy-3''-18F-fluorothymidine PET predicts response to (V600E)BRAF-targeted therapy in preclinical models of colorectal cancer. J Nucl Med, 54(3), 424-30, 2013.
- Xie, J, Wang, C, Virostko, J, Manning, HC, Pham, W, Bauer, J, Gore, JC A novel reporter system for molecular imaging and high-throughput screening of anticancer drugs. Chembiochem, 14(12), 1494-503, 2013.
- Katsha, A, Soutto, M, Sehdev, V, Peng, D, Washington, MK, Piazuelo, MB, Tantawy, MN, Manning, HC, Lu, P, Shyr, Y, Ecsedy, J, Belkhiri, A, El-Rifai, W Aurora Kinase A Promotes Inflammation and Tumorigenesis in Mice and Human Gastric Neoplasia. Gastroenterology, 2013.
- McKinley, ET, Liu, H, McDonald, WH, Luo, W, Zhao, P, Coffey, RJ, Hanks, SK, Manning, HC Global phosphotyrosine proteomics identifies PKC¿¿ as a marker of responsiveness to Src inhibition in colorectal cancer. PLoS One, 8(11), e80207, 2013.
- McKinley, ET, Ayers, GD, Smith, RA, Saleh, SA, Zhao, P, Washington, MK, Coffey, RJ, Manning, HC Limits of [18F]-FLT PET as a biomarker of proliferation in oncology. PLoS One, 8(3), e58938, 2013.
- Walsh, AJ, Cook, RS, Manning, HC, Hicks, DJ, Lafontant, A, Arteaga, CL, Skala, MC Optical metabolic imaging identifies glycolytic levels, subtypes, and early-treatment response in breast cancer. Cancer Res, 73(20), 6164-74, 2013.
- Tang, D, McKinley, ET, Hight, MR, Uddin, MI, Harp, JM, Fu, A, Nickels, ML, Buck, JR, Manning, HC Synthesis and Structure-Activity Relationships of 5,6,7-Substituted Pyrazolopyrimidines: Discovery of a Novel TSPO PET Ligand for Cancer Imaging. J Med Chem, 56(8), 3429-33, 2013.
- Thompson, MM, Manning, HC, Ellacott, KL Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. PLoS One, 8(11), e79980, 2013.
- Xu, J, Li, K, Smith, RA, Waterton, JC, Zhao, P, Chen, H, Does, MD, Manning, HC, Gore, JC Characterizing tumor response to chemotherapy at various length scales using temporal diffusion spectroscopy. PLoS One, 7(7), e41714, 2012.
- Wyatt, SK, Manning, HC, Bai, M, Ehtesham, M, Mapara, KY, Thompson, RC, Bornhop, DJ Preclinical molecular imaging of the translocator protein (TSPO) in a metastases model based on breast cancer xenografts propagated in the murine brain. Curr Mol Med, 12(4), 458-66, 2012.
- Myers, MV, Manning, HC, Coffey, RJ, Liebler, DC Protein expression signatures for inhibition of epidermal growth factor receptor-mediated signaling. Mol Cell Proteomics, 11(2), M111.015222, 2012.
- Tang, D, Hight, MR, McKinley, ET, Fu, A, Buck, JR, Smith, RA, Tantawy, MN, Peterson, TE, Colvin, DC, Ansari, MS, Nickels, M, Manning, HC Quantitative Preclinical Imaging of TSPO Expression in Glioma Using N,N-Diethyl-2-(2-(4-(2-18F-Fluoroethoxy)Phenyl)-5,7-Dimethylpyrazolo[1,5-a]Pyrimidin-3-yl)Acetamide. J Nucl Med, 53(2), 287-94, 2012.
- Buck, JR, Saleh, S, Uddin, MI, Manning, HC Rapid, Microwave-Assisted Organic Synthesis of Selective (V600E)BRAF Inhibitors for Preclinical Cancer Research. Tetrahedron Lett, 53(32), 4161-4165, 2012.
- Yankeelov, TE, Peterson, TE, Abramson, RG, Garcia-Izquierdo, D, Arlinghaus, LR, Li, X, Atuegwu, NC, Catana, C, Manning, HC, Fayad, ZA, Gore, JC Simultaneous PET-MRI in oncology: a solution looking for a problem. Magn Reson Imaging, 30(9), 1342-56, 2012.
- McKinley, ET, Smith, RA, Tanksley, JP, Washington, MK, Walker, R, Coffey, RJ, Manning, HC [(18)F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in M¿¿n¿¿trier''s disease. Ann Nucl Med, 26(9), 757-63, 2012.
- McKinley, ET, Bugaj, JE, Zhao, P, Guleryuz, S, Mantis, C, Gokhale, PC, Wild, R, Manning, HC 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res, 17(10), 3332-40, 2011.
- Fox, EM, Miller, TW, Balko, JM, Kuba, MG, SÃ¡nchez, V, Smith, RA, Liu, S, GonzÃ¡lez-Angulo, AM, Mills, GB, Ye, F, Shyr, Y, Manning, HC, Buck, E, Arteaga, CL A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res, 71(21), 6773-84, 2011.
- Guo, N, Xie, J, Manning, HC, Deane, NG, Ansari, MS, Coffey, RJ, Gore, J, Price, RR, Baldwin, RM, McIntyre, JO A novel in vitro assay to assess phosphorylation of 3''-[(18)F]fluoro-3''-deoxythymidine. Mol Imaging Biol, 13(2), 257-64, 2011.
- Miller, TW, Balko, JM, Fox, EM, Ghazoui, Z, Dunbier, A, Anderson, H, Dowsett, M, Jiang, A, Smith, RA, Maira, SM, Manning, HC, GonzÃ¡lez-Angulo, AM, Mills, GB, Higham, C, Chanthaphaychith, S, Kuba, MG, Miller, WR, Shyr, Y, Arteaga, CL ERÎ±-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov, 1(4), 338-351, 2011.
- Gore, JC, Manning, HC, Quarles, CC, Waddell, KW, Yankeelov, TE Magnetic resonance in the era of molecular imaging of cancer. Magn Reson Imaging, 29(5), 587-600, 2011.
- Smith, RA, Guleryuz, S, Manning, HC Molecular imaging metrics to evaluate response to preclinical therapeutic regimens. Front Biosci, 16393-410, 2011.
- Hight, MR, Nolting, DD, McKinley, ET, Lander, AD, Wyatt, SK, Gonyea, M, Zhao, P, Manning, HC Multispectral fluorescence imaging to assess pH in biological specimens. J Biomed Opt, 16(1), 016007, 2011.
- Buck, JR, McKinley, ET, Hight, MR, Fu, A, Tang, D, Smith, RA, Tantawy, MN, Peterson, TE, Colvin, D, Ansari, MS, Baldwin, RM, Zhao, P, Guleryuz, S, Manning, HC Quantitative, Preclinical PET of Translocator Protein Expression in Glioma Using 18F-N-Fluoroacetyl-N-(2,5-Dimethoxybenzyl)-2-Phenoxyaniline. J Nucl Med, 52(1), 107-14, 2011.
- Garrett, JT, Olivares, MG, Rinehart, C, Granja-Ingram, ND, SÃ¡nchez, V, Chakrabarty, A, Dave, B, Cook, RS, Pao, W, McKinely, E, Manning, HC, Chang, J, Arteaga, CL Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc Natl Acad Sci U S A, 108(12), 5021-6, 2011.
- Tang, D, Buck, JR, Hight, MR, Manning, HC Microwave-assisted Organic Synthesis of a High-affinity Pyrazolo-pyrimidinyl TSPO Ligand. Tetrahedron Lett, 51(35), 4595-4598, 2010.
- Ayers, GD, McKinley, ET, Zhao, P, Fritz, JM, Metry, RE, Deal, BC, Adlerz, KM, Coffey, RJ, Manning, HC Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements. J Ultrasound Med, 29(6), 891-901, 2010.
- Virostko, J, Xie, J, Hallahan, DE, Arteaga, CL, Gore, JC, Manning, HC A Molecular Imaging Paradigm to Rapidly Profile Response to Angiogenesis-directed Therapy in Small Animals. Mol Imaging Biol, 2009.
- Sexton, M, Woodruff, G, Cudaback, E, Kreitzer, FR, Xu, C, Lin, YH, MÃ¶ller, T, Bai, M, Manning, HC, Bornhop, D, Stella, N Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO. PLoS One, 4(12), e8271, 2009.
- Yankeelov, TE, Avison, MJ, Damon, BM, Manning, HC, Peterson, TE, Gore, JC Frontiers of Biomedical Imaging Science 2009: workshop report and research opportunities. Cancer Res, 69(20), 7902-4, 2009.
- Shah, C, Miller, TW, Wyatt, SK, McKinley, ET, Olivares, MG, Sanchez, V, Nolting, DD, Buck, JR, Zhao, P, Ansari, MS, Baldwin, RM, Gore, JC, Schiff, R, Arteaga, CL, Manning, HC Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer. Clin Cancer Res, 15(14), 4712-21, 2009.
- Miller, TW, Forbes, JT, Shah, C, Wyatt, SK, Manning, HC, Olivares, MG, Sanchez, V, Dugger, TC, de Matos Granja, N, Narasanna, A, Cook, RS, Kennedy, JP, Lindsley, CW, Arteaga, CL Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Clin Cancer Res, 15(23), 7266-76, 2009.
- Wyatt, SK, Manning, HC, Bai, M, Bailey, SN, Gallant, P, Ma, G, McIntosh, L, Bornhop, DJ Molecular Imaging of the Translocator Protein (TSPO) in a Pre-Clinical Model of Breast Cancer. Mol Imaging Biol, 2009.
- Peterson, TE, Manning, HC Molecular imaging: 18F-FDG PET and a whole lot more. J Nucl Med Technol, 37(3), 151-61, 2009.
- Manning, HC, Shay, SD, Mericle, RA Multispectral molecular imaging of capillary endothelium to facilitate preoperative endovascular brain mapping. J Neurosurg, 2009.
- Manning, HC, Lander, A, McKinley, E, Mutic, NJ Accelerating the Development of Novel Molecular Imaging Probes: A Role for High-Throughput Screening. J Nucl Med, 2008.
- Manning, HC, Merchant, NB, Foutch, AC, Virostko, JM, Wyatt, SK, Shah, C, McKinley, ET, Xie, J, Mutic, NJ, Washington, MK, Lafleur, B, Tantawy, MN, Peterson, TE, Ansari, MS, Baldwin, RM, Rothenberg, ML, Bornhop, DJ, Gore, JC, Coffey, RJ Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer. Clin Cancer Res, 14(22), 7413-7422, 2008.
- H. Charles Manning "Optical imaging shines in vivo." Journal of Nuclear Medicine, 4923N-29N, 2008.
- Deane, NG, Manning, HC, Foutch, AC, Washington, MK, Aronow, BA, Bornhop, DJ, Coffey, RJ Targeted imaging of colonic tumors in smad3-/- mice discriminates cancer and inflammation. Mol Cancer Res, 5(4), 341-9, 2007.
- Manning, HC, Smith, SM, Sexton, M, Haviland, S, Bai, M, Cederquist, K, Stella, N, Bornhop, DJ A peripheral benzodiazepine receptor targeted agent for in vitro imaging and screening. Bioconjug Chem, 17(3), 735-40, 2006.
- Smentek, L, Andes Hess, B, Cross, JP, Charles Manning, H, Bornhop, DJ Density-functional theory structures of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complexes for ions across the lanthanide series. J Chem Phys, 123(24), 244302, 2005.
- Manning, HC., Bai, M., Anderson, BM., Lisiak, R., Samuelson, L., Bornhop, D.J "Expeditious synthesis of P-Protected macrocycles in-route to lanthanide chelate metal complexes." Tetrahedron Letters, 464707-4710, 2005.
- Manning, HC, Goebel, T, Thompson, RC, Price, RR, Lee, H, Bornhop, DJ Targeted molecular imaging agents for cellular-scale bimodal imaging. Bioconjug Chem, 15(6), 1488-95, 2004.
- Marcu, L., Vernier, T., Manning, H.C., Salemi, S., Li, A., Craft, C., Gundersen, M., Bornhop, D "Fluorescence microscopy studies of a peripheral-benzodiazepine-receptor-targeted molecular probe for brain tumor imaging.." Proceedings of SPIE-The International Society for Optical Engineering, 514164-69, 2003.
- Manning, HC., Skwierawska, A., Marx, JN., et al "Rapid removal of benzyloxycarbonyl groups from 1,4,7,10-tetraazacyclododecane derivatives by catalytic transfer hydrogenation." Synthetic Communications, 33(3), 457-461, 2003.
- Manning, HC, Goebel, T, Marx, JN, Bornhop, DJ Facile, efficient conjugation of a trifunctional lanthanide chelate to a peripheral benzodiazepine receptor ligand. Org Lett, 4(7), 1075-8, 2002.
- Griffin, JMM., Skwierawska, AM., Manning, HC., Marx, JN., Bornhop, DJ "Simple, high-yielding synthesis of trifunctional fluorescent lanthanide chelates." Tetrahedron Letters, 423823-3825, 2001.